The sterilization of surgical supplies and parenteral drugs is a carefully controlled process. An effective commonly used method of sterilization is by steam under pressure. However, many surgical instruments and supplies are adversely affected by heat. Sterilization at high temperatures is not practical for such items.
An outgrowth of agricultural and industrial fumigation is sterilization utilizing gaseous ethylene oxide. The advantages of sterilization utilizing ethylene oxide include, sterilization at lower temperatures thereby avoiding the detrimental effect of elevated temperatures on the goods to be sterilized, items to be sterilized can be terminally sterilized in their packages, and the equipment required to carry out the process is simple.
The preferred method of utilizing ethylene oxide in sterilization process has been to dilute the ethylene oxide with a gas inert to the ethylene oxide, such as Freon.RTM., a fluoro-chloro substituted ethane or CO.sub.2. The Freon.RTM. selected should be a gas at the sterilization temperature. Generally, the concentration of ethylene oxide is about 450 mg/lt to about 1,500 mg./lt, while processing temperatures can range from about 70.degree. to about 140.degree. F. Preferably, where the diluent is Freon.RTM., the ethylene oxide concentration is about 12 wt. %. in the sterilant gas. Where the diluent is CO.sub.2, the concentration of ethylene oxide is about 10 wt. %. For such processes, the parameters which affect ethylene oxide sterilization processes are exposure time, gas concentration, temperature and humidity. For diluted ethylene oxide, relative humidities below 30% RH limit the effectiveness of the ethylene oxide sterilization process. High humidities, e.g., above 90% RH, also results in inadequate processing.
The classical method for determining whether or not a particular sterilization process has been effective is to include in the system exposed to the sterilizing process a suitable resistant organism. For ethylene oxide sterilization the organism of choice is spores of Bacillus subtilis var. niger, since these spores exhibit high resistance to ethylene oxide. Such a control method suffers from the fact that at least several days are required to culture the spores in order to confirm the effectiveness of the sterilization process. Additionally, the spores being living organisms, the rate at which they are killed is a logarithmic relationship with time, resulting in a broad time window between initial and complete spore kill.
In the field of sterilization by heat various physical indicators have been developed to monitor the sterilization process. These devices vary in quality from the simplest melt indicators which show whether or not a particular temperature has been achieved to more sophisticated devices such as PymaH Corporations Thermalog.RTM. S, which integrates the time, temperature and steam exposure parameters of the sterilization process. Similarly, various physical indicators have been developed for monitoring the ethylene oxide sterilization process.
An indicator comprising 4(4-nitrobenzyl)pyridine applied to a paper strip has been used in ethylene oxide sterilization process monitoring; see for example Journal of Pharmaceutical Sciences, Brewer et al., pages 57-59, January 1966. Other compounds, including pyridines and quinolines have also been utilized; see U.S. Pat. No. 3,627,469. An ink composition has been prepared as a telltale for ethylene oxide sterilization which utilizes the fact that MgCl.sub.2 reacts with ethylene oxide to produce a base, Mg(OH).sub.2, which is detected by a pH sensitive dye; see U.S. Pat. No. 3,098,751. This same chemical reaction has been used to prepare a physical sterilization indicator by depositing reactants on an absorbent material and enclosing the composition in a sealed envelope of gas permeable film such as polyethylene; see Royce and Bower "An Indicator Control Device for ethylene Oxide Sterilization." J. Pharm. and Pharm. 111 Suppl. 294T-298T.
A more recent development in the area of ethylene oxide monitoring is disclosed in U.S. Pat. No. 4,138,216. The device disclosed comprises a wick impregnated with MgCl.sub.2 and a pH sensitive dye is enclosed in a gas impervious envelop having one end open. An additional constituent is an acidic material, e.g., tartaric acid, which acts as a quantifier to adjust the time response of the device. This latter device is particularly useful in ethylene oxide sterilization monitoring because it is responsive to humidity levels as well as temperature and gas concentration.
As a result of the environmental problems attendant to discarding the spent ethylene oxide sterilant gas mixture, there has been a trend toward using 100% ethylene oxide in the sterilization process. The primary advantage is that the sterilant gas can be recycled. In contrast, in order to recycle the diluted ethylene oxide sterilant which is prevalent in the field, the concentration of ethylene oxide must be determined and appropriate amount of the gas added to the sterilant stream in order to bring it to specification. These added steps mitigate against recycling the diluted gas. Unfortunately, the prior art devices do not offer the performance desired when the sterilant gas comprises 100% ethylene oxide.